ClinVar Miner

Submissions for variant NM_000430.4(PAFAH1B1):c.22C>T (p.Arg8Ter)

dbSNP: rs121434489
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000008549 SCV000194369 pathogenic Lissencephaly due to LIS1 mutation 2014-03-31 criteria provided, single submitter clinical testing
Institute of Human Genetics, University of Leipzig Medical Center RCV000008549 SCV001429446 pathogenic Lissencephaly due to LIS1 mutation 2023-12-06 criteria provided, single submitter clinical testing Criteria applied: PVS1, PM2_SUP, PS4_MOD. This variant was detected in a mosaic state (allele fraction in blood 0.12)
Institute of Human Genetics, University of Leipzig Medical Center RCV001255338 SCV001431668 likely pathogenic Intellectual disability 2020-08-03 criteria provided, single submitter clinical testing The variant c.22C>T, p.(Arg8*) was identified in an individual with neurodevelopmental disorder (NDD) and classified as Likely pathogenic according to ACMG guidelines. Inheritance for this variant was mosaic (12-13% allele frequency).The variant likely explains the NDD in this individual.
Labcorp Genetics (formerly Invitae), Labcorp RCV001851741 SCV002243755 pathogenic not provided 2021-12-02 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg8*) in the PAFAH1B1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PAFAH1B1 are known to be pathogenic (PMID: 1671808, 11115846, 14581661). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with lissencephaly (PMID: 14581661, 29671837). ClinVar contains an entry for this variant (Variation ID: 8081). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV001851741 SCV005079525 pathogenic not provided 2024-04-07 criteria provided, single submitter clinical testing Previously reported as a mosaic variant in an individual with subcortical band heterotopia, and in the heterozygous state in individuals with lissencephaly (PMID: 14581661, 29671837, 34979677); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 32366993, 15719169, 29671837, 22129557, 33484635, 33911214, 34979677, 14581661)
OMIM RCV000008548 SCV000028756 pathogenic Subcortical band heterotopia 2003-10-28 no assertion criteria provided literature only
OMIM RCV000008549 SCV000028757 pathogenic Lissencephaly due to LIS1 mutation 2003-10-28 no assertion criteria provided literature only
University of Washington Center for Mendelian Genomics, University of Washington RCV001291182 SCV001479605 likely pathogenic Lissencephaly no assertion criteria provided research

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